Toluene → HCID 58689699, compound

Participants

Reaction Conditions

Reaction Steps

Powdered sodium hydroxide (7.2 g, 180 mmol) was dissolved in water (15 mL). The solution was allowed to cool to ambient temperature before addition of intermediate (a) (R)-1-chloro-3-(2-methoxyphenyl)-2-propanol(6.0 g, 30.0 mmol) in methanol (20 mL+2×5 mL washes) via dropping funnel. After stirring for 5 mins 2-aminoethane hydrogen sulfate (16.9 g, 120 mmol) was added in portions over 5 mins and the reaction mixture heated to 40° C. After 2 hrs, toluene (75 mL) and powdered sodium hydroxide (7.2 g, 180 mmol) were added and the reaction heated to 65° C. and stirred for 17 hrs. The mixture was cooled, diluted with water (300 mL) and extracted with toluene (2×150 mL). The combined organics were washed with water (slowly separating emulsion obtained) and brine, dried (Na2SO4) and concentrated under reduced pressure to afford the crude product as a pale yellow oil (5.21 g). Purification by column chromatography (silica: ethyl acetate/ethanol/triethylamine, 79/20/1 ratio) afforded intermediate (d), (R)-2-(2-methoxybenzyl)morpholine as a colorless oil (6.04 g, 50% yield).

Provenance & Evidence